Chloroacetic Acid → 5-(Chloromethyl)-3-(3-fluorophenyl)-1,2,4-oxadiazole

HRID 1724080노트

반응식

HRID 1724080 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][OH:8])=[NH:6].[Cl:12][CH2:13][C:14](O)=O.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C>[Cl:12][CH2:13][C:14]1[O:8][N:7]=[C:5]([C:4]2[CH:9]=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[N:6]=1

참가 물질

7

반응물 4

HCID 300Chloroacetic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178513300HCID 178513300, 화합물

생성물 1

HCID 167362485-(Chloromethyl)-3-(3-fluorophenyl)-1,2,4-oxadiazole수율 60%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매2회

실험 절차

3-Fluoro-N-hydroxy-benzamidine (1.4 g, 9.08 mmol), chloroacetic acid (0.94 g, 9.99 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.91 g, 9.99 mmol) and 1-hydroxybenzotriazole hydrate (1.35 g, 9.99 mmol) were mixed in N,N-dimethylformamide (15 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (50 mL), washed with water (50 mL), washed with aqueous saturated sodium bicarbonate (75 mL), washed with water again (50 mL) and washed with brine (50 mL). The organic phase was dried over sodium sulfate and concentrated to give a solid. The solid was dissolved in N,N-dimethylformamide (10 mL) and the reaction mixture stirred at 120° C. for 1.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), washed with water (3×50 mL) and washed with brine (50 mL). The organic phase was dried over sodium sulfate and concentrated. The residue was purified on silica gel eluting with 10 to 30% ethyl acetate in hexanes to give the product as a yellow oil (1.15 g, 60%). 1H NMR (300 MHz, CDCl3): δ 7.91 (dd, 1H), 7.82 (m, 1H), 7.5 (m, 1H), 7.25 (m, 1H), 4.78 (s, 2H).

후처리

  1. washwashed with water (50 mL)
  2. washwashed with aqueous saturated sodium bicarbonate (75 mL)
  3. washwashed with water again (50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto give a solid
  8. stirringthe reaction mixture stirred at 120° C. for 1.5 hours
  9. temperatureThe reaction mixture was cooled to room temperature
  10. washwashed with water (3×50 mL)
  11. washwashed with brine (50 mL)
  12. dry with materialThe organic phase was dried over sodium sulfate
  13. concentrationconcentrated
  14. customThe residue was purified on silica gel eluting with 10 to 30% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-9ee59a655278447586bd451e1a816580
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07485722B2

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